伊马替尼衍生物的合成及细胞毒活性研究
收稿日期: 2015-06-25
修回日期: 2015-07-27
网络出版日期: 2015-08-26
基金资助
黑龙江省教育厅科学技术研究(No. 12521417)资助项目.
Synthesis and Cytotoxic Activity of Imatinib Derivatives
Received date: 2015-06-25
Revised date: 2015-07-27
Online published: 2015-08-26
Supported by
Project supported by the Foundation of Heilongjiang Educational Committee (No. 12521417).
以3-乙酰基嘧啶、2-甲基-5-硝基苯胺为起始原料, 经加成、缩合、环化、还原得到中间体 N-(2-甲基-5-氨基苯基)-4-(3-吡啶基)嘧啶-2-胺(6), 再与(L)-N-酰化-氨基酸缩合得到14个伊马替尼氨基酸衍生物7a～7n. 目标化合物结构经过IR, 1H NMR, 13C NMR, HRMS等确证. 采用四甲基偶氮唑盐(MTT)法考察了目标化合物对人白血病细胞(K562)、人肺癌细胞(A549)、人肝癌细胞(HepG-2)体外抑制活性测试. 结果显示化合物7a,7d,7e,7i,7j,7k,7l,7n体外抑制活性较高, 与对照品伊马替尼相近.
关键词： 伊马替尼衍生物; 合成; 四甲基偶氮唑盐(MTT)法
陈仕杰 , 和龙 , 王雪微 , 龚显峰 , 张华 . 伊马替尼衍生物的合成及细胞毒活性研究[J]. 有机化学, 2015 , 35(11) : 2377 -2382 . DOI: 10.6023/cjoc201506030
Fourteen derivatives of imatinib have been prepared by condensation of (L)-N-acylation amino acid with N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidine amine (6), which was prepared from 3-acetyl-pyrimidin and 2-methyl-5-nitroaniline through the reactions of addition, condensation, cyclization and reduction, respectively. The structures of all target compounds were characterized by IR, 1H NMR, 13C NMR and HRMS techniques. They were evaluated for cytotoxic activity against human Leukemia cells (K562), human non-small-cell-lung cancer cells lines (A549) and human hepatoma cell lines (HepG-2) by methyl thiazolyl tetrazolium (MTT) method. The results showed the cytotoxic activities of compounds 7d,7i,7j,7k,7l, 7n against human Leukemia cells (K562) and human non-small-cell-lung cancer cell lines (A549), compounds 7a, 7d,7e against human hepatoma cell lines (HepG-2) were comparable to those of imatinib.
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